Early Fasting Serum Glucose or Weight Reduction With Tirzepatide and Metabolic Outcomes in People With Type 2 Diabetes: A Post Hoc Analysis of the SURPASS Trials

OBJECTIVE To evaluate late (week 40 or 42; hereafter, week 40/42) metabolic outcomes by early glycemic response (<20% or ≥20% fasting serum glucose [FSG] reduction at week 4) or weight response (<5% or ≥5% weight reduction at week 8), respectively, in tirzepatide-treated participants with type 2 diabetes in the SURPASS trials. RESEARCH DESIGN AND METHODS This post hoc analysis used pooled data across trials. Baseline characteristics, change from baseline to week 40/42 for efficacy parameters, and gastrointestinal (GI) adverse events (AEs) were described and analyzed by early response in terms of FSG (SURPASS-1 to -4; n = 3,676) or weight (SURPASS-1 to -5; n = 4,121) in the efficacy and safety analysis set, respectively. RESULTS Early responders in FSG (50%) were younger, with higher glycemic parameters and lower weight at baseline. Early responders in weight (31%) had lower glycemic parameters and weight at baseline, and a greater percentage were women and White. Early versus nonearly responders in FSG or weight achieved better HbA1c (−2.6% vs. −2.0% or −2.5% vs. −2.2%, respectively) and weight (−11% vs. −10% or −15% vs. −8%, respectively) responses at week 40/42 and greater improvements in blood pressure and lipids profile. Nonearly responders also had clinically meaningful HbA1c and weight reductions with all tirzepatide doses. The incidence of GI AEs (generally mild to moderate events) decreased over time and was, in general, comparable between early and nonearly responders. CONCLUSIONS Both early glucose and weight responses with tirzepatide were associated with better longer-term metabolic outcomes. Early response may be a good clinical indicator that could help inform treatment individualization to achieve therapeutic goals.